Response of Preterm Newborns to Immunization With a Hexavalent Diphtheria–Tetanus–Acellular Pertussis–Hepatitis B Virus–Inactivated Polio and Haemophilus influenzae Type b Vaccine: First Experiences and Solutions to a Serious and Sensitive Issue

Objective. Preterm infants are at in- creased risk from infections and should be vaccinated at the usual chronological age. The aim of the study was to evaluate the immunogenicity and reactogenicity of a hexavalent diphtheria-tetanus-acellular pertussis-hepa- titis B virus-inactivated polio and Haemophilus influen- zae type b (DTPa-HBV-IPV/Hib) vaccine in preterm in- fants. Methods. In a comparative trial, 94 preterm infants between 24 and 36 weeks (mean SD gestational age: 31.05 3.45 weeks; mean birth weight: 1420 600 g) and a control group of 92 full-term infants were enrolled to receive 3 doses of a DTPa-HBV-IPV/Hib vaccine at 2, 4, and 6 months. Immunogenicity was assessed in serum samples that were taken before and 4 weeks after pri- mary vaccination. Evaluation of reactogenicity was based on diary cards. Results. All preterm (n 93) and full-term (n 89) infants who were included in the immunogenicity anal- ysis had seroprotective titers to diphtheria; tetanus; and polio virus types 1, 2, and 3. The immune response to the Hib and hepatitis B components was lower in preterm than in full-term infants: 92.5% versus 97.8% and 93.4% versus 95.2%, respectively. Vaccine response rates for pertussis antigens were >98.9% in both study groups. Although most geometric mean titers were lower in pre- term infants, titers were similar for pertussis, a major threat for premature infants. The vaccine was well toler- ated, and there were no differences in reactogenicity between groups. Some extremely immature infants expe- rienced transient cardiorespiratory events within the 72 hours after the first vaccination with no clinical reper- cussion. Conclusions. Preterm infants who were immunized with the hexavalent DTPa-HBV-IPV/Hib vaccine at 2, 4, and 6 months displayed good immune response to all antigens. The availability of this vaccine greatly facili- tates the vaccination of premature infants. Pediatrics 2005;116:1292-1298; preterm infants immunization, com- bined vaccines, DTPa-HBV-IPV/Hib vaccine. ABBREVIATIONS. DTPa-HBV-IPV/Hib, diphtheria-tetanus- acellular pertussis- hepatitis B virus-inactivated polio and Hae- mophilus influenzae type b; GA, gestational age; HBsAg, hepatitis B surface antigen; IU, international unit; PT, pertussis toxin; FHA, filamentous hemagglutinin; PRN, pertactin; PRP, Haemophilus in- fluenzae type b polysaccharide; NU, neonatology unit; GMT, geo- metric mean titer; GMC, geometric mean concentrations; wP, whole-cell pertussis.